The proposed population-based, statewide study of Alzheimer disease (AD) among California Seventh-day Adventists is designed to provide incidence/prevalence data and information about risk factors for AD using a case-control methodology. A two-phase study is proposed. During Phase 1 (Study Year 01) we will further develop, field test, strictly evaluate, and refine the substantive procedures of the proposed case-ascertainment and diagnosis methodology in a defined geographic area. During Phase 2 (Study Years 02-05) we will ascertain all potential cases of AD and other dementias among California Adventists, collect the necessary clinical information and determine the diagnosis of AD or another dementia for these patients, and conduct a case-control study among a random sample of 600 white California Adventists. Four approaches will be used to ascertain potential AD cases; through the Adventist churches; through public announcements in Adventist publications and church-affiliated broadcast media; through the Adventist Health System (AHS); and through family interviews. Necessary diagnostic clinical information will be collected by specially designated and trained AHS physicians and other physicians or by an Alzheimer's Disease Research Center or a California Alzheimer's Disease Diagnosis & Treatment Center. The training will be accomplished by a practice-integrated continuing medical education program. Proactive assistance to these physicians will be the responsibility of the chief study neurologist and the Study Diagnostic Panel. Prevalence and incidence rates of AD will be estimated for all Adventists in California, for each sex, for Whites, Blacks, Hispanics and Orientals and for various geographic regions. A prior gender and ethnic hypotheses will be tested. Other comparisons will be made. during Phase 1 the feasibility of using blood and non-blood relatives as controls will be determined. If not feasible, matched church controls will be used. Detailed information concerning exposure/events related to medical history, family history, dietary habits, toxins, travel and zoonoses will be collected. Both confirmatory and exploratory case-control analyses of putative rusk factors for AD will be conducted. The primary biostatistical methodology for estimating odds ratios will be matched, multivariate, conditional logistic regression with stepwise inclusion of variables. Adventists will make an excellent population in which to study the etiology of AD. The church hierarchy is enthusiastically supportive and, from previous experience, the Adventists themselves will also be enthusiastically supportive. Adventists are proud of their lifestyle and health habits and have proven that they are willing subjects for health-related studies. Another reason for their anticipated participation is the fact that the study subjects and their families will receive direct benefits through (1) the identification of reversible or treatable dementias and (2) the provision of important information concerning caregiving and support agencies and groups. This study will be the largest population-based study to provide descriptive and analytic epidemiologic and clinical data on AD and other dementias to date. The study will allow a priori hypotheses to be tested as well as new hypotheses to be generated. Potential future work includes; linkage studies if potential informative pedigrees are identified; population-based genetic- environmental etiologic studies; and a longitudinal study of a cohort of non-demented subjects with extensive exposure histories obtained by the present project.